Autosomal trisomy is the most common type of chromosome abnormality in humans, occurring in at least 3-4% of newborns having an additional chromosome 13, 18 or 21, but the vast majority of autosomal trisomies are eliminated prenatally and account for approximately 25% of all clinically recognized spontaneous abortions. Despite their high rate of occurrence and obvious clinical importance, surprisingly little is known about factors which result in autosomal trisomy. Cytogenetic studies of their parental origin have shown that the additional chromosome can arise from an error involving any one of the four parental divisions, although an error at maternal meiosis I is by far the most frequent. However, there is considerable variation in non-disjunctional patterns among individual trisomies, the basis of this variation being unknown. Furthermore, it is not known if the errors leading to trisomy involve faulty chromosome pairing and/or separation or even whether the primary event involves the chromosome itself, the spindle or another cellular organelle. The recent identification of restriction fragment length polymorphisms on all human chromosomes now makes it possible to study many of these questions, and this approach is especially efficacious if the molecular information is combined with cytogenetic observations. In the proposed research we will compare appropriate chromosome heteromorphisms and restriction fragment length polymorphisms (RFLPs) in trisomic conceptions, both spontaneously aborted and liveborn, and their parents in order to: 1) determine the contribution of errors in pairing to the genesis of autosomal trisomy. Centromere distances of RFLPs will be compared between trisomic and control populations to test the hypothesis that elimination of crossing-over or altered levels of crossing-over are important in the etiology of trisomy. 2) determine the parent and meiotic stage of origin of autosomal trisomy and assess the variation in origin among the trisomies involving different autosomes.